Our laboratory has continued to investigate the control of the onset of puberty in male sexual development using the primate model. Significant findings establish the validity of some of our earlier hypotheses. These include the following: 1) Using time series analysis we have demonstrated no change in frequency of gonadotropin pulses, rather an alteration in amplitude during pubertal development. 2) GnRH pulsing is decreased during prepubertal life; however, we have shown that very large GnRH pulses can occur during this period. 3) Even in the absence of gonadal feedback, we have found increases in amplitude of gonadotropin pulses. 4) During pubertal development we have found significant changes in the ratio of bioassayable vs radioimmunoassayable LH. 5) Longitudinal studies have demonstrated significant individual differences in the timing of puberty. 6) Electron and light microscopic histological changes in the testis have been correlated with pulsatile hormonal secretion during sexual development. Independent of changes during the pubertal process in vivo, we have demonstrated alterations in the sensitivity of Sertolic cell FSH receptors and other metabolic cellular functions in vitro. In another series of experiments, we have uncovered a short 11-15 minute ultradian rhythm in gonadotropin pulsing. In addition, using newly synthesized potent GnRH antagonists, we have demonstrated rapid effects and different dose-responses in both castrate and intact animals. One further study has demonstrated a paradoxical effect of increased doses of the newly discovered human pancreatic tumor growth factor on GH release. In our clinical studies, we have described Gh neurosecretory dysfunction as the etiology of the short stature in some children who do not have GH deficiency. This abnormality relates to our observations in both irradiated monkeys and humans. In another clinical study we discovered a circhoral rhythm in urinary gonadotropin secretion in male children during pubertal development.